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Sauer MM, Tortorici MA, Park YJ, et al. Structural basis for broad coronavirus neutralization. bioRxiv. 2021;doi: 10.1101/2020.12.29.424482.
Sauer, M. M., Tortorici, M. A., Park, Y. J., Walls, A. C., Homad, L., Acton, O., Bowen, J., Wang, C., Xiong, X., de van der Schueren, W., Quispe, J., Hoffstrom, B. G., Bosch, B. J., McGuire, A. T., & Veesler, D. (2021). Structural basis for broad coronavirus neutralization. bioRxiv : the preprint server for biology, . https://doi.org/10.1101/2020.12.29.424482
Sauer, Maximilian M, et al. "Structural basis for broad coronavirus neutralization." bioRxiv : the preprint server for biology vol. (2021). doi: https://doi.org/10.1101/2020.12.29.424482
Sauer MM, Tortorici MA, Park YJ, Walls AC, Homad L, Acton O, Bowen J, Wang C, Xiong X, de van der Schueren W, Quispe J, Hoffstrom BG, Bosch BJ, McGuire AT, Veesler D. Structural basis for broad coronavirus neutralization. bioRxiv. 2021 Jan 04; doi: 10.1101/2020.12.29.424482. PMID: 33398277; PMCID: PMC7781312.
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bioRxiv. 2021 Jan 04; doi: 10.1101/2020.12.29.424482.

Structural basis for broad coronavirus neutralization.

bioRxiv : the preprint server for biology

Maximilian M Sauer, M Alexandra Tortorici, Young-Jun Park, Alexandra C Walls, Leah Homad, Oliver Acton, John Bowen, Chunyan Wang, Xiaoli Xiong, Willem de van der Schueren, Joel Quispe, Benjamin G Hoffstrom, Berend-Jan Bosch, Andrew T McGuire, David Veesler

Affiliations

  1. Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
  2. Institut Pasteur, Unité de Virologie Structurale, Paris, France; CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
  3. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
  4. Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  6. Antibody Technology Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
  7. Department of Global Health, University of Washington, Seattle, WA 98195, USA.
  8. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.

PMID: 33398277 PMCID: PMC7781312 DOI: 10.1101/2020.12.29.424482

Abstract

Three highly pathogenic β-coronaviruses crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. SARS-CoV-2 has infected more than 64 million people worldwide, claimed over 1.4 million lives and is responsible for the ongoing COVID-19 pandemic. We isolated a monoclonal antibody, termed B6, cross-reacting with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses, and broadly inhibiting entry of pseudotyped viruses from two coronavirus lineages. Cryo-electron microscopy and X-ray crystallography characterization reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery and indicate that antibody binding sterically interferes with spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages along with proof-of-concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-coronavirus vaccine.

Conflict of interest statement

Declaration of interests M.M.S, M.A.T., Y.J.P., A.C.W, A.T.M. and D.V. are named as inventors on patent applications filed by the University of Washington based on the studies presented in this paper.

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